1. Field of the Invention
New, improved antibiotics are continually in demand. In addition to antibiotics which are useful for human diseases, improved antibiotics are also needed in the veterinary field. Improved growth promotion in animals is one important goal for these antibiotics. Growth promotion is achieved, for example, by reducing disease and by increasing feed-utilization efficiency.
Coccidiosis is one disease important to veterinary science, especially to the poultry industry. Coccidiosis results from infection by one or more species of Eimeria or Isopora (for a summary see Lund and Farr in "Diseases of Poultry," 5th ed., Biester and Schwarte, Eds., Iowa State University Press, Ames, Iowa, 1965, pp 1056-1096). Economic losses due to coccidiosis are great, and known anticoccidial agents have many disadvantages. Improved anticoccidial agents continue to be needed.
Promotion of growth in ruminants, such as cattle, is another economically-desirable objective of veterinary science. Of particular interest is growth promotion which is achieved by increasing feed-utilization efficiency. The mechanism for utilization of the major nutritive portion (carbohydrates) of ruminant feeds is well known. Microorganisms in the rumen of the animal degrade carbohydrates to produce monosaccharides and then convert these monosaccharides to pyruvate compounds. Pyruvates are metabolized by microbiological processes to form acetates, butyrates or propionates, collectively known as volatile fatty acids (VFA). For a more detailed discussion, see Leng in "Physiology of Digestion and Metabolism in the Ruminant," Phillipson et al., Eds., Oriel Press, Newcastle-upon-Tyne, England, 1970, pp 408-410.
The relative efficiency of VFA utilization is discussed by McCullough in Feedstuffs, June 19, 1971, page 19; Eskeland et al. in J. An. Sci. 33, 282 (1971); and Church et al. in "Digestive Physiology and Nutrition of Ruminants," Vol. 2, 1971, pp 622 and 625. Although acetates and butyrates are utilized, propionates are utilized with greater efficiency. A beneficial compound, therefore, stimulates animals to produce a higher proportion of propionates from carbohydrates, thereby increasing carbohydrate-utilization efficiency.
2. The Prior Art
A-32887 is a new member of the group of polyether antibiotics. Examples of members of this group include monensin (U.S. Pat. No. 3,501,568); dianemycin [R. L. Hamill, M. M. Hoehn, G. E. Pittenger, J. Chamberlin, and M. Gorman, J. Antibiotics 22, 161 (1969)]; nigericin [L. K. Steinrauf, Mary Pinkerton, and J. W. Chamberlin, Biochem. Biophys. Res. Comm. 33, 29 (1968)]; salinomycin (U.S. Pat. No. 3,857,948); A-130-A (U.S. Pat. No. 3,903,264); A-28695 A and B (U.S. Pat. No. 3,839,558); grisorixin [Chem. Commun., p. 1421 (1970)]; A-218 and K-41 [J. Antibiotics 29 (1), 10-14 (1976)].
Of this group of antibiotics, A-32887 is most closely related to K-41. A convenient method for distinquishing A-32887 from K-41 is by chromatography. A-32887 can be separated from K-41, for example, by silica-gel thin-layer chromatography in the following two systems (R.sub.f values are approximate):
______________________________________ Antibiotic Solvent System R.sub.f Value ______________________________________ A-32887 chloroform:methanol 0.78 (92:8) K-41 chloroform:methanol 0.84 (92:8) A-32887 ethyl acetate:ethanol 0.76 (1:4) K-41 ethyl acetate:ethanol 0.70 (1:4) ______________________________________